PURPOSE Detection of bacteria-specific metabolism via positron emission tomography (PET) is an emerging strategy to image human pathogens, with dramatic implications for clinical practice. In silico and in vitro screening tools have recently been applied to this problem, with several monosaccharides including l-arabinose showing rapid accumulation in Escherichia coli and other organisms. Our goal for this study was to evaluate several synthetically viable arabinofuranose-derived 18 F analogs for their incorporation into pathogenic bacteria. PROCEDURES We synthesized four radiolabeled arabinofuranose-derived sugars: 2-deoxy-2-[18 F]fluoro-arabinofuranoses (d-2-18 F-AF and l-2-18 F-AF) and 5-deoxy-5-[18 F]fluoro-arabinofuranoses (d-5-18 F-AF and l-5-18 F-AF). The arabinofuranoses were synthesized from 18 F- via triflated, peracetylated precursors analogous to the most common radiosynthesis of 2-deoxy-2-[18 F]fluoro-d-glucose ([18 F]FDG). These radiotracers were screened for their uptake into E. coli and Staphylococcus aureus. Subsequently, the sensitivity of d-2-18 F-AF and l-2-18 F-AF to key human pathogens was investigated in vitro. RESULTS All 18 F radiotracer targets were synthesized in high radiochemical purity. In the screening study, d-2-18 F-AF and l-2-18 F-AF showed greater accumulation in E. coli than in S. aureus. When evaluated in a panel of pathologic microorganisms, both d-2-18 F-AF and l-2-18 F-AF demonstrated sensitivity to most gram-positive and gram-negative bacteria. CONCLUSIONS Arabinofuranose-derived 18 F PET radiotracers can be synthesized with high radiochemical purity. Our study showed absence of bacterial accumulation for 5-substitued analogs, a finding that may have mechanistic implications for related tracers. Both d-2-18 F-AF and l-2-18 F-AF showed sensitivity to most gram-negative and gram-positive organisms. Future in vivo studies will evaluate the diagnostic accuracy of these radiotracers in animal models of infection.

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用于检测病原微生物的阿拉伯呋喃糖衍生的正电子发射断层扫描放射性示踪剂

目的通过正电子发射断层扫描 (PET) 检测细菌特异性代谢是一种新兴的人类病原体成像策略，对临床实践具有重大意义。计算机模拟和体外筛选工具最近已应用于这个问题，包括 l-阿拉伯糖在内的几种单糖在大肠杆菌和其他生物体中显示出快速积累。我们本研究的目标是评估几种合成可行的阿拉伯呋喃糖衍生的 18 F 类似物，以便将它们掺入病原菌中。程序我们合成了四种放射性标记的阿拉伯呋喃糖衍生糖：2-deoxy-2-[18 F]fluoro-arabinofuranoses（d-2-18 F-AF 和 l-2-18 F-AF）和 5-deoxy-5-[ 18 F]氟-阿拉伯呋喃糖（d-5-18 F-AF和l-5-18 F-AF）。阿拉伯呋喃糖是由 18 F-通过三氟甲磺酸酯合成的，类似于最常见的 2-脱氧-2-[18 F]氟-d-葡萄糖（[18 F]FDG）放射合成的全乙酰化前体。筛选这些放射性示踪剂是否被大肠杆菌和金黄色葡萄球菌吸收。随后，在体外研究了 d-2-18 F-AF 和 l-2-18 F-AF 对关键人类病原体的敏感性。结果 所有 18 F 放射性示踪剂靶标均以高放射化学纯度合成。在筛选研究中，d-2-18 F-AF 和 l-2-18 F-AF 在大肠杆菌中的积累量高于金黄色葡萄球菌。当在一组病理微生物中进行评估时，d-2-18 F-AF 和 l-2-18 F-AF 都表现出对大多数革兰氏阳性菌和革兰氏阴性菌的敏感性。结论 阿拉伯呋喃糖衍生的 18 F PET 放射性示踪剂可以以高放射化学纯度合成。我们的研究表明 5 取代的类似物没有细菌积累，这一发现可能对相关示踪剂具有机械意义。d-2-18 F-AF 和 l-2-18 F-AF 对大多数革兰氏阴性和革兰氏阳性生物都表现出敏感性。未来的体内研究将评估这些放射性示踪剂在感染动物模型中的诊断准确性。